TY - JOUR
T1 - Novel myelofibrosis treatment strategies
T2 - potential partners for combination therapies
AU - Stein, B. L.
AU - Swords, R.
AU - Hochhaus, A.
AU - Giles, F.
N1 - Funding Information:
Financial support for medical assistance was provided by Novartis Pharmaceuticals. We thank Daniel Hutta and Matthew Hoelzle for their medical editorial assistance with this manuscript.
Publisher Copyright:
© 2014, Macmillan Publishers Limited.
PY - 2014/11
Y1 - 2014/11
N2 - Of the myeloproliferative neoplasms (MPNs), myelofibrosis (MF) is associated with the greatest symptom burden and poorest prognosis and is characterized by constitutional symptoms, cytopenias, splenomegaly and bone marrow fibrosis. A hallmark of MF is dysregulation of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway that has led to the development of JAK inhibitors targeting this pathway. Calreticulin gene mutations have recently been identified in JAK2 mutation-negative patients with MF. Identification of JAK inhibitor resistance and broad contributions to MF disease pathogenesis from epigenetic deregulators, pathways that work in concert with JAK/STAT (that is, mammalian target of rapamycin/AKT/phosphoinositide 3-kinase, RAS/RAF/MEK, PIM kinase), fibrosis-promoting factors and the MF megakaryocyte, suggest that numerous options may be partnered with a JAK inhibitor. Therefore, we will discuss logical and potential partners for combination therapies for the treatment of patients with MF.
AB - Of the myeloproliferative neoplasms (MPNs), myelofibrosis (MF) is associated with the greatest symptom burden and poorest prognosis and is characterized by constitutional symptoms, cytopenias, splenomegaly and bone marrow fibrosis. A hallmark of MF is dysregulation of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway that has led to the development of JAK inhibitors targeting this pathway. Calreticulin gene mutations have recently been identified in JAK2 mutation-negative patients with MF. Identification of JAK inhibitor resistance and broad contributions to MF disease pathogenesis from epigenetic deregulators, pathways that work in concert with JAK/STAT (that is, mammalian target of rapamycin/AKT/phosphoinositide 3-kinase, RAS/RAF/MEK, PIM kinase), fibrosis-promoting factors and the MF megakaryocyte, suggest that numerous options may be partnered with a JAK inhibitor. Therefore, we will discuss logical and potential partners for combination therapies for the treatment of patients with MF.
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U2 - 10.1038/leu.2014.176
DO - 10.1038/leu.2014.176
M3 - Review article
C2 - 24888274
AN - SCOPUS:85027918531
SN - 0887-6924
VL - 28
SP - 2139
EP - 2147
JO - Leukemia
JF - Leukemia
IS - 11
ER -
